A single-center analysis of the survival benefits of adjuvant gemcitabine chemotherapy for biliary tract cancer

Background

Surgical resection is the only curative treatment of biliary tract cancer (BTC). However, the prognosis of BTC remains unsatisfactory. The aim of this study is to evaluate the benefits of adjuvant gemcitabine chemotherapy for BTC.

Methods

We performed a historical cohort study that involved 198 patients who underwent R0 surgical resection. Patients who underwent major hepatectomy were administered biweekly intravenous gemcitabine at a dose of 800 mg/m². Otherwise, patients were administered intravenous gemcitabine at a dose of 1,000 mg/m² in 3 weekly infusions, which were followed by a 1-week pause. The primary outcome was overall survival. The hazard ratio (HR) of adjuvant chemotherapy was estimated by propensity score-stratified Cox regression that was adjusted for confounders.

Results

Forty patients received adjuvant chemotherapy. The HR of adjuvant chemotherapy was 0.47 [95 % confidence interval (CI) 0.28–0.95; P = 0.03]. Subgroup analysis showed that the survival benefits were possibly modified by lymph node positivity (HR 0.19; 95 % CI 0.07–0.58; interaction, P = 0.22), stage III (HR 0.11; 95 % CI 0.02–0.50; interaction, P < 0.01), intrahepatic cholangiocarcinoma (ICC) (HR 0.09; 95 % CI 0.01–0.67; interaction, P = 0.05), and poorly differentiated tumor (HR 0.16; 95 % CI 0.03–0.85; interaction, P = 0.13).

Conclusions

Adjuvant gemcitabine chemotherapy for BTC may be effective, particularly for patients with stage III and ICC.     

Interferon-inducible guanylate binding protein (GBP2) is associated with better prognosis in breast cancer and indicates an efficient T cell response

Background

Recently, interferon-inducible guanylate binding protein (GBP2) has been discussed as a possible control factor in tumor development, which is controlled by p53, and inhibits NF-Kappa B and Rac protein as well as expression of matrix metalloproteinase 9. However, the potential role that GBP2 plays in tumor development and prognosis has not yet been studied.

Methods

We analyzed whether GBP2 mRNA levels are associated with metastasis-free interval in 766 patients with node negative breast carcinomas who did not receive systemic chemotherapy. Furthermore, response to anthracycline-based chemotherapy was studied in 768 breast cancer patients.

Results

High expression of GBP2 in breast carcinomas was associated with better prognosis in the univariate (P < 0.001, hazard ratio 0.763, 95 % CI 0.650–0.896) as well as in the multivariate Cox analysis (P = 0.008, hazard ratio 0.731, 95 % CI 0.580–0.920) adjusted to the established clinical factors age, pT stage, grading, hormone and ERBB2 receptor status. The association was particularly strong in subgroups with high proliferation and positive estrogen receptor status but did not reach significance in carcinomas with low expression of proliferation associated genes. Besides its prognostic capacity, GBP2 also predicted pathologically complete response to anthracycline-based chemotherapy (P = 0.0037, odds ratio 1.39, 95 % CI 1.11–1.74). Interestingly, GBP2 correlated with a recently established T cell signature, indicating tumor infiltration with T cells (R = 0.607, P < 0.001).

Conclusion

GBP2 is associated with better prognosis in fast proliferating tumors and probably represents a marker of an efficient T cell response.     

XRCC1 and GSTP1 polymorphisms and prognosis of oxaliplatin-based chemotherapy in colorectal cancer: a meta-analysis

Purpose

Genetic variations are related to individual differences of DNA repair ability and drug metabolism, which can greatly influence prognosis of antineoplastic agents, such as oxaliplatin. The aim was to explore the influences of X-ray repair cross-complementing 1(XRCC1) and Glutathione S-transferase P1 (GSTP1) genetic variants on prognosis of oxaliplatin-based chemotherapy in colorectal cancer patients.

Methods

We performed a meta-analysis including 13 original studies with a total number of 1,234 patients in advanced or metastatic colorectal cancer. Tumor responses [complete response, partial response, stable disease (SD) and progressive disease (PD)] and progression-free survival were estimated.

Results

Our results showed that XRCC1 Arg399Gln polymorphism was significantly associated with tumor chemotherapy when SD or PD was considered as non-response [risk ratio (RR) = 1.29; 95 % confidence intervals (CI): 1.05–1.60; P = 0.02]. No significant association was found between GSTP1 Ile105 Val polymorphism and tumor response (RR = 0.63; 95 % CI: 0.35–1.14; P = 0.13). In addition, our results also showed that there was no significant association between XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes and hazard ratio for progression-free survival (Hazards ratio = 1.04 and 1.92; 95 % CI: 0.75–1.43 and 0.62–1.37; P = 0.826 and 0.677, respectively).

Conclusion

In our meta-analysis, XRCC1 Arg399Gln polymorphism may be a valuable genetic marker for oxaliplatin-based chemotherapy in colorectal cancer, and the results still need further confirmation.     

Overexpression of retinoic acid-induced protein 3 predicts poor prognosis for hepatocellular carcinoma

Aim

To investigate clinical significance of retinoic acid-induced protein 3 (RAI3) in hepatocellular carcinoma (HCC).

Methods

Expression of RAI3 at both mRNA and protein levels in tumor, para-tumor and normal liver tissues was detected in 106 HCC patients by real-time quantitative RT-PCR, Western blot and immunohistochemistry. Then, the correlation of RAI3 expression with clinicopathological characteristics and survivals of HCC patients was analyzed.

Results

Our data first found that RAI3 mRNA and protein expression were both significantly higher in HCC than in para-tumor (both P < 0.001) and normal liver tissues (both P < 0.001). The correlation analysis showed a positive correlation between RAI3 mRNA level and RAI3 protein level in HCC tissues (r = 0.8, P < 0.001). Immunohistochemistry data also revealed that overexpression of RAI3 was present in 73.6 % (78/106) of HCC tissues. In addition, high RAI3 protein expression was correlated with advanced TNM stage (P = 0.001), high serum AFP (P = 0.008), vascular invasion (P = 0.01) and tumor recurrence (P = 0.008). Moreover, HCC patients with overexpression of RAI3 had significantly shorter overall (P = 0.01) and disease-free survival (P = 0.01). Furthermore, multivariate analysis showed that overexpression of RAI3 was an independent prognostic factor for both overall (P = 0.02) and disease-free survival (P = 0.03) in HCC.

Conclusion

Our data for the first time provide a basis for the concept that overexpression of RAI3 may contribute to the malignant progression of HCC and predict poor prognosis for patients with this deadly disease after curative hepatectomy. RAI3 might be an important marker for tumor progression and prognosis, as well as a potential therapeutic target of HCC.     

Increased expression of α5β1-integrin is a prognostic marker for patients with gastric cancer

Objective

The study was to evaluate the association of expression level of α5β1-integrin with clinicopathologic features and prognosis in gastric cancer (GC).

Methods

The expression of α5β1-integrin in normal gastric mucosa and GC tissue was detected with immunohistochemistry. The level of α5 and β1 mRNA in GC tissues and non-neoplastic tissues was evaluated in 48 paired cases by quantitative real-time polymerase chain reaction (qRT-PCR). Survival analysis by the Kaplan–Meier method was performed to assess prognostic significance.

Results

The α5β1-integrin expression was detected in 68.3 % (127/186) GC samples, and there was a significant difference on their positive expression rate between GC tissue and normal gastric mucosa (P < 0.001). The positive expression rate of α5β1-integrin in patients with poor histologic differentiation (P = 0.001), lymph node metastasis (P < 0.001), and recurrence (P < 0.001) group was heightened. Using Kaplan–Meier analysis, a comparison of survival curves of low versus high expresser of α5β1-integrin revealed a highly significant difference in human GC tissue (P = 0.002), which suggested that overexpression of α5β1-integrin is associated with a worse prognosis. Multivariate analyses showed that α5β1-integrin expression was independent risk factor predicting overall survival [Hazard ratio (HR) 1.594, 95 % confidence interval (CI) 1.236–2.408, P = 0.006] and disease-free survival [HR 3.952, 95 % CI 1.676–9.861, P = 0.003] in GC.

Conclusions

The α5β1-integrin promotes angiogenesis and associates with lymph node metastasis, vascular invasion and poor prognosis of GC. The current study shows that α5β1-integrin may be an independent prognostic factor for GC patients.     

Diffusion-weighted imaging reflects pathological therapeutic response and relapse in breast cancer

Background

Conventional imaging does not always accurately depict the pathological response to neoadjuvant chemotherapy (NAC). Diffusion-weighted imaging (DWI) may provide additional insight into the chemotherapeutic effect. This study assessed whether the apparent diffusion coefficient (ADC) correlated with pathological outcome and prognosis in breast cancer patients receiving NAC.

Methods

Fifty-six patients with locally advanced breast cancer received surgery after NAC. Dynamic contrast-enhanced (DCE) and DWI were performed before and after NAC. The pathological response was classified into five categories from no response to complete response according to amount of residual cancer. The correlation between ADC and postoperative pathologic and prognostic outcome was assessed.

Results

The distribution of the pathological response classification was as follows: no response, 3 cases; mild response, 22 cases; moderate response, 12 cases; marked response, 11 cases; complete response, 8 cases. ADC after NAC correlated with pathological response, but ADC before NAC did not. The change in ADC after chemotherapy had better correlation coefficient (r = 0.67) than change in size (r = 0.58) and ADC after NAC (r = 0.64). Although the group with larger change of tumor size showed only marginal significance compared with the smaller change group (p = 0.089), the group with higher change of ADC showed significantly better prognosis than the lower one (p = 0.038).

Conclusions

Change in ADC after chemotherapy better correlated with pathological outcome and prognosis than change in tumor size. DWI has potential in evaluating the pathological outcome of NAC in breast cancer patients.     

Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment

Background

The purpose of this study was to evaluate the impact of human epidermal growth factor receptor 2 (HER2) status and trastuzumab treatment on the prognosis of patients with advanced gastric cancer (AGC).

Methods

We retrospectively analyzed 364 AGC patients who received systemic chemotherapy. To evaluate the impact of trastuzumab exposure during any type of chemotherapy, our analysis used time-varying covariates to avoid a possible lead-time bias.

Results

Among the 364 patients, 58 (15.9 %) were HER2-positive. The median overall survival of the HER2-positive patients treated with trastuzumab (n = 43) was significantly longer than that of the HER2-negative patients [n = 306; 24.7 vs. 13.9 months, with an adjusted hazard ratio (HR) of 0.58; 95 % confidence interval (CI), 0.36–0.95; P = 0.03]. Notably, 22 patients continued with trastuzumab beyond the date of progression. By contrast, the HER2-positive patients not treated with trastuzumab (n = 15) showed survival similar to that of the HER2-negative patients (13.5 vs. 13.9 months, with an adjusted HR of 1.04; 95 % CI, 0.52–2.11; P = 0.91). According to the multivariate analysis, exposure to trastuzumab was independently associated with a better prognosis (HR 0.56; 95 % CI; 0.33–0.93; P = 0.026).

Conclusions

Recent HER2-positive AGC patients have a better prognosis than HER2-negative patients, particularly when treated with trastuzumab.     

Clinicopathologic characteristics and survival of male breast cancer

Backgrounds

Male breast cancer (MBC) is a rare disease and accounts for <1 % of all breast cancers.

Methods

We retrospectively analyzed clinicopathologic characteristics and prognosis of MBC patients who were diagnosed in our hospital between March 2002 and March 2012.

Results

The median age of diagnosis of MBC was 62 years, which was 9 years older than female breast cancer (FBC) patients. The highest proportion of MBC patients was in the 50–59-year age group. The percentage of invasive ductal carcinoma in MBC was much higher than in FBC (P = 0.000). The positive rate of estrogen receptors in MBC patients (87.9 %) was significantly higher than in FBC patients (P = 0.048), whereas HER-2 was positive in 17.2 % of MBC patients, which was significantly lower than in FBC patients (P = 0.001). There was a consistent significant difference in luminal subtypes of FBC and MBC patients (P = 0.000). The overall survival rates of MBC were significantly higher than FBC (P = 0.004). HER-2-positive patients had a statistically worse prognosis than HER-2-negative patients (P = 0.040). Lymph node metastasis and larger tumor size were also associated with poorer prognosis (P = 0.056 and P = 0.088). The level of hormones was examined in 7 patients, and abnormal hormone levels were detected in 4.

Conclusion

The FBC patients were significantly different from the MBC in clinicopathologic and prognostic characteristics. HER-2 positivity was an important factor for prognosis.     

Prognostic predictors and spread patterns in adult ovarian granulosa cell tumors: a multicenter long-term follow-up study of 108 patients

Purpose

To identify prognostic predictors and spread patterns in adult ovarian granulosa cell tumors (OGCTs).

Methods

Available retrospective data of 108 OGCT patients managed at three centers between January 1, 1991 and December 31, 2010 were abstracted and analyzed.

Results

Stage distributions at diagnosis for stage I, II and III OGCT were 84.3, 5.4, and 9.3 %, respectively. Optimal cytoreduction with no macroscopically visible disease was achieved in 99/108 (91.6 %) patients. The median disease-free interval to first recurrence was 61 months. The overall 5- and 10-year survival rates were 93.3 and 90.9 %, respectively. Disease recurred in 18 (16.6 %) patients, and 8 (7.4 %) patients died of their disease. The first recurrence sites included the pelvic peritoneum (n = 10), liver/liver-capsule (n = 5), rectosigmoid colon (n = 4), retroperitoneal lymph nodes (n = 3), omentum (n = 3), small bowel mesenterium (n = 2), and vaginal cuff (n = 2). Multiple-site recurrence was observed in 9/18 (50 %) patients. Secondary cytoreduction requiring extensive surgery was performed in 14 patients with an optimality rate of 71.4 %. The remaining four patients received only chemotherapy. Multivisceral approaches, including pelvic peritonectomy (n = 9; 64.2 %), rectosigmoid resection (n = 3; 21.4 %), and segmental liver capsule resection (n = 2; 14.2 %) were performed more frequently during the secondary surgery. Definitive retroperitoneal lymph node metastasis rates at the initial and recurrent settings were 5.1 % (3/58) and 21.4 % (3/14), respectively. Both stage and residual tumor status were significantly associated with recurrence in univariate and multivariate analyses.

Conclusions

Stage and residual tumor status are predictors of recurrence. Pelvic peritoneal, nodal and hepatic involvement, and multiple-site spread patterns requiring extensive cytoreductive surgery are likely associated with recurrence of OGCTs.     

Prognostic role of microRNA polymorphisms in patients with advanced esophageal squamous cell carcinoma receiving platinum-based chemotherapy

Purpose

MicroRNA (miRNA) polymorphisms contribute to cancer susceptibility and prognosis. The aim of this study was to evaluate the effects of miRNA polymorphisms on clinical outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) treated with platinum-based chemotherapy.

Methods

Five polymorphisms (miR-146a rs2910164, miR-196a2 rs11614913, miR-100 rs1834306, miR-125a rs12976445 and miR-26a1 rs7372209) were genotyped in 378 patients with advanced ESCC recruited at Zhongshan Hospital. The associations between genotypes and drug response, toxicity, and overall survival were analyzed.

Results

miR-146a rs2910164 was significantly associated with an increased risk of severe hematological toxicity [odds ratio = 0.374, 95 % confidence interval (CI) 0.171–0.819, P = 0.014]. The TT genotypes of both miR-196a2 rs11614913 and miR-125a rs12976445 were associated with worse survival [hazard ratio (HR) = 1.552, 95 % CI 1.112–2.165, P = 0.010; HR = 2.171, 95 % CI 1.173–4.017, P = 0.014, respectively]. Combined analysis revealed a 4.073-fold increased risk of death in patients carrying two unfavorable genotypes (P = 0.002).

Conclusions

Taken together, these findings indicate that miRNA polymorphisms may predict prognosis in advanced ESCC patients receiving platinum-based chemotherapy.     

Validity of response assessment criteria in neoadjuvant chemotherapy for gastric cancer (JCOG0507-A)

Background

Neoadjuvant chemotherapy may improve outcomes in gastric cancer. Tumor responses can be evaluated with RECIST, Japanese Classification of Gastric Carcinoma (JCGC), and histological criteria. These approaches have not yet been compared.

Methods

We analyzed two phase II trials of neoadjuvant chemotherapy using S-1 plus cisplatin. JCOG0210 included patients with linitis plastica and large ulcero-invasive tumors, whereas JCOG0405 comprised those with para-aortic or bulky lymph node metastases. Radiologic evaluations were conducted using RECIST in JCOG0405 and JCGC criteria in JCOG0210, because the latter included many patients without measurable lesions. A histological responder was defined as a patient in whom one third or more of the tumor was affected. The hazard ratios (HR) for death between responders and non-responders and response rate differences between short- and long-term survivors were estimated.

Results

In JCOG0210 (n = 49), HR was 0.54 in JCGC responders (P = 0.059) and 0.40 in histological responders (P = 0.005). The difference in response rates between short- and long-term survivors using histological criteria (34 %, P = 0.023) was greater than that using JCGC criteria (24 %, P = 0.15). In JCOG0405 (n = 51), HR was 0.67 in RECIST responders (P = 0.35) and 0.39 in histological responders (P = 0.030). In short- and long-term survivors, respectively, RECIST response rates were 62  and 67 % (P = 0.77), whereas histological response rates were 33  and 63 % (P = 0.048).

Conclusions

Histological criteria showed higher response assessment validity than RECIST or JCGC criteria and yielded the best surrogate endpoint for overall survival.     

Prognostic significance of peritoneal lavage cytology in patients with colorectal cancer

Background

The clinical significance of peritoneal lavage cytology for patients with gastric cancer is recognized, whereas that for patients with colorectal cancer remains controversial. The present study used a nationwide registry to clarify the prognostic significance of peritoneal lavage cytology in patients with colorectal cancer.

Methods

We retrospectively analyzed factors associated with recurrence and survival in patients with T3–T4 colorectal cancer without distant metastasis taken from the nationwide registry of the Japanese Society for Cancer of the Colon and Rectum between 1984 and 1999.

Results

Among 34,554 patients in this study, not all of whom received peritoneal lavage cytology, 35 had positive peritoneal lavage cytology. Gender (P = 0.0004), tumor location (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion (P < 0.0001), lymph node metastasis (P < 0.0001) and peritoneal cytology (P = 0.015) were risk factors for peritoneal recurrence. Multivariate analysis revealed that tumor location (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion (P < 0.0001) and lymph node metastasis (P < 0.0001) were independent risk factors for peritoneal metastasis. Gender (P < 0.0001), tumor location (P < 0.0001), age (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion (P < 0.0001), lymph node metastasis (P < 0.0001) and peritoneal cytology (P = 0.0004) were independent prognostic factors according to the Cox proportional hazards model.

Conclusion

Positive peritoneal lavage cytology was associated with poorer survival in patients with stage II and III colorectal cancer. Positive cytology might be a good indicator of candidates for intensive adjuvant chemotherapy. The benefit of intensive adjuvant chemotherapy for such patients should be validated in prospective trials.     

The significant increase and dynamic changes of the myeloid-derived suppressor cells percentage with chemotherapy in advanced NSCLC patients

Purpose

To investigate the correlations between myeloid-derived suppressor cells (MDSCs) in the peripheral blood and cancer stage, immune function, and chemotherapy.

Methods

Percentages of MDSCs (CD11b⁺CD14^?CD33⁺ cells) and lymphocyte subsets in peripheral blood mononuclear cells (PBMCs) of 94 patients with Non-small cell lung cancer (NSCLC) who were treated naïve and 30 healthy individuals were measured. Changes of the MDSCs percentage were further detected in patients with advanced NSCLC treated with systemic chemotherapy. Finally, coculture with CD8⁺ cells was developed to determine effect of MDSCs on IFN-γ secretion of T lymphocytes.

Results

MDSCs percentage of 94 patients with NSCLC was significantly higher than that of 30 healthy subjects (P < 0.05), the percentages were increased with tumor progression, in patients with stage III and IV percentages were significantly higher than those in stage I and II patients (P = 0.013). The MDSCs percentage was negatively related to percentage of CD8⁺ cells in the peripheral blood (r = ?0.354, n = 38, P = 0.029), and when they were cocultured, IFN-γ secretion of CD8⁺ cells was significantly decreased (P < 0.05). In 20 patients with advanced NSCLC who received systemic chemotherapy, nine partial remission (PR) cases got MDSCs percentage significantly decreased (P < 0.001), three stable disease (SD) cases remained invariable (P = 0.307) and eight progressive disease (PD) cases got significantly increased (P = 0.024).

Conclusion

The percentage of MDSCs in the patients was significantly higher than that of the healthy control subjects and it increased with tumor progression partially by inhibiting the CD8⁺ cell function. The dynamic changes of MDSCs percentage reflected the efficacy of systemic chemotherapy.     

A matched-pair comparison of intensity-modulated radiation therapy with cetuximab versus intensity-modulated radiation therapy with platinum-based chemotherapy for locally advanced head neck cancer

Purpose

We retrospectively compared the efficacy of intensity-modulated radiotherapy (IMRT) and cetuximab (IMRT/cetuximab) versus IMRT and platinum-based chemotherapy (IMRT/platinum) for locally advanced head neck squamous cell carcinoma (LAHNSCC).

Methods

Thirty-one IMRT/cetuximab patients were matched 1:2 with 62 IMRT/platinum patients according to primary site and clinical stage. The primary endpoint was locoregional recurrence (LRR), and secondary endpoints included distant metastasis (DM), cause-specific survival (CSS), and overall survival (OS).

Results

Because of inherent selection bias, the IMRT/cetuximab cohort was significantly older and with a higher Charlson Comorbidity Index. IMRT/cetuximab and IMRT/platinum did not have significantly different LRR and DM (33 vs. 23 % at 2 years, P = 0.22; 17 vs. 11 % at 2 years, P = 0.40; respectively). IMRT/cetuximab had significantly worse CSS and OS (67 vs. 84 %, P = 0.04; 58 vs. 83 %, P = 0.001; respectively). However, for the subset of elderly patients ≥65 years old, there is no difference between the two cohorts for all endpoints (all P = NS).

Conclusion

IMRT/platinum should remain the preferred choice of chemoradiotherapy for LAHNSCC, but IMRT/cetuximab may be a reasonable alternative for elderly patients.     

Donor interleukin 6 gene polymorphisms predict the recurrence of hepatocellular carcinoma after liver transplantation

Background

Application of the Milan criteria is an effective strategy to select patients with hepatocellular carcinoma (HCC) for liver transplantation, but HCC recurrence is still a major concern. The aim of this study was to determine whether interleukin 6 (IL6) polymorphisms and clinical variables are potential predictors for HCC recurrence and prognosis after transplantation.

Methods

A total of 110 consecutive patients with HCC undergoing liver transplantation were enrolled in the study. Six tag single nucleotide polymorphisms in IL6 were genotyped in both the donors and recipients. Demographic characteristics, HCC features, and IL6 polymorphisms were assessed against HCC recurrence.

Results

Pretransplant hepatitis B virus DNA (P = 0.014), pretransplant serum alpha-fetoprotein (P = 0.035), number of nodules (P = 0.011), diameter of main nodule (P = 0.001), macrovascular invasion (P = 0.001), microvascular invasion (P = 0.001), HCC exceeding the Milan criteria (P < 0.001), and donor rs2069852 AA genotype (P = 0.010) were associated with HCC recurrence. Recurrence-free survival rate and overall survival rate were significantly lower (P = 0.011 and P = 0.026, respectively) in patients whose donor had the rs2069852 AA genotype than in those whose donor had the AG and GG genotypes. Independent risk factors for recurrence-free survival and overall survival were microvascular invasion (P = 0.003; P = 0.002), HCC exceeding the Milan criteria (P < 0.001; P = 0.001), and donor rs2069852 AA genotype (P = 0.002; P = 0.010).

Conclusions

Our data suggest that donor IL6 rs2069852 polymorphisms may be a potential genetic marker for HCC recurrence after liver transplantation in the Han Chinese population.

     

Lymph node ratio is a critical prognostic predictor in gastric cancer treated with S-1 chemotherapy

Background

S-1 is an oral anticancer drug widely used in postoperative adjuvant therapy for patients in Japan with stage II/III gastric cancer. Candidates for more intense adjuvant treatments need to be identified, particularly among patients with stage III cancer.

Methods

Univariate and multivariate analyses were conducted for patients with stage II/III gastric cancer who underwent surgery and received S-1 postoperatively between 2000 and 2010.

Results

Factors indicating poor prognosis identified by univariate analysis include male sex (P = 0.022), age ≥67 years (P = 0.021), intestinal-type histology (P = 0.049), lymph node ratio ≥16.7 % (P < 0.0001), open surgery (P = 0.039), as well as the 13th JGCA stage (P < 0.0001) and the 14th JGCA/7th International Union Against Cancer (UICC) stage (P < 0.0001). Multivariate analysis revealed that lymph node ratio ≥16.7 % and intestinal-type histology were significant as predictors of prognosis, independent from the pathological stages. Based on these and other findings, stage IIIC cancer on the 14th JGCA/7th UICC stage system in combination with the lymph node ratio could identify patients with extremely high risk for recurrence

Conclusions

Our current findings suggest that lymph node ratio ≥16.7 % in combination with the new staging system could be a useful prognostic indicator in advanced gastric cancer. Because these high-risk patients cannot be identified preoperatively by any diagnostic tool, further improvement in postoperative adjuvant therapy is warranted.     

Two-year adjuvant imatinib mesylate after complete resection of localized, high-risk GIST with KIT exon 11 mutation

Purpose

To evaluate the efficacy and safety of 2-year adjuvant imatinib for patients at high risk of recurrence after complete resection of localized gastrointestinal stromal tumor with KIT exon 11 mutation.

Methods

Imatinib 400 mg/d was administered until disease recurrence, intolerable toxicities, or for 2 years. The primary end point was recurrence-free survival.

Results

Patients (n = 47) from 4 centers in Korea were enrolled. Treatment was well tolerated. Grade 3–4 toxicities included neutropenia (27.7 %), skin rash (8.5 %), anorexia (4.3 %), and constipation (2.1 %). At a median follow-up of 56.7 months, 19 patients had recurrences. Median recurrence-free survival was 58.9 months, which was significantly longer than 22.7 months from historical data of 27 patients in the pre-imatinib era (P < 0.0001). Imatinib was rechallenged for 15 patients with recurrence after completion of adjuvant imatinib. Thirteen patients had partial response, and two had stable disease. There was only one death so far.

Conclusions

Postoperative adjuvant imatinib for 2 years was safe and could prolong the recurrence-free survival in patients with a high risk of recurrence after complete resection of localized KIT exon 11 mutated gastrointestinal stromal tumor. Reintroduction of imatinib after recurrence appears to be effective if the recurrence develops after completion of adjuvant imatinib.     

Comparison of advanced adenocarcinomas of esophagogastric junction and distal stomach in Japanese patients

Background

There have been no reports on the incidence, characteristics, treatment outcomes, and prognosis of inoperably advanced or recurrent adenocarcinoma of the esophagogastric junction (AEGJ) in Japan.

Methods

We investigated the clinicopathological characteristics, treatment outcomes, and prognosis for 816 patients with esophagogastric junctional and gastric adenocarcinoma who received first-line chemotherapy between 2004 and 2009.

Results

Of 816 patients, 82 (10 %) had AEGJ. The patients with AEGJ had significantly more lung and lymph node metastasis, but less peritoneal metastasis, than those with gastric adenocarcinoma (GAC). The objective response rate to first-line chemotherapy was 23.3 % for patients with AEGJ and 22.6 % in patients with GAC (p = 0.90). The median survival was 13.0 months in AEGJ and 11.8 months in GAC (p = 0.445). In no patient was tumor site a significant prognostic factor (p = 0.472). In patients with AEGJ, ECOG PS ≥ 2, presence of liver metastasis, and absence of lung metastasis were significantly associated with poor prognosis.

Conclusions

No significant differences were observed in treatment outcomes between advanced AEGJ and GAC. Therefore, the same chemotherapy regimen can be given as a treatment arm in future Japanese clinical trials to both patients with inoperably advanced or recurrent AEGJ and those with GAC.     

Correlation between expressions of ERCC1/TS mRNA and effects of gastric cancer to chemotherapy in the short term

Purpose

To study the correlation between expression levels of ERCC1/TS mRNA and the susceptibility of preoperative chemotherapy for patients with gastric cancer.

Methods

A total of forty cases with advanced gastric cancer of T3–4N1–2M0 were treated with preoperative chemotherapy according to FLEEOX regimen based on endarterial-intravenous coadministration. Sufficient, fresh gastric tissue specimens were obtained with the help of gastroscope, and the expression levels of ERCC1/TS mRNA were detected by qRT-PCR before chemotherapy. The chemotherapeutic response was evaluated with Choi Criteria after chemotherapy, and pathologic remission extent was observed after surgery. The correlation between the expression levels of ERCC1/TS mRNA before chemotherapy and the chemotherapeutic effect based on imageology and pathology was analyzed.

Results

The response rate of Chemotherapy in this cohort was 80.0 % based on imageology and 51.43 % based on pathology. The expression levels of ERCC1/TS mRNA were significantly associated with imageology remission extent (P = 0.033, P = 0.025) and pathologic remission extent (P = 0.044, P = 0.016), respectively. The chemotherapeutic effect on patients with low-expression levels of ERCC1/TS mRNA was better.

Conclusions

From the perspective of pathology and imageology evaluating the preoperative chemotherapeutic response for patients with gastric cancer, ERCC1 and TS were used as the molecular predictors and provided prognostic information in this study.